Haematologica (Apr 2022)
Molecular characterization and clinical outcome of B-cell precursor acute lymphoblastic leukemia with IG-MYC rearrangement
- Simon Bomken,
- Amir Enshaei,
- Edward C. Schwalbe,
- Aneta Mikulasova,
- Yunfeng Dai,
- Masood Zaka,
- Kent T.M. Fung,
- Matthew Bashton,
- Huezin Lim,
- Lisa Jones,
- Nefeli Karataraki,
- Emily Winterman,
- Cody Ashby,
- Andishe Attarbaschi,
- Yves Bertrand,
- Jutta Bradtke,
- Barbara Buldini,
- G.A. Amos Burke,
- Giovanni Cazzaniga,
- Gudrun Gohring,
- Hesta A. de Groot-Kruseman,
- Claudia Haferlach,
- Luca Lo Nigro,
- Mayur Parihar,
- Adriana Plesa,
- Emma Seaford,
- Edwin Sonneveld,
- Sabine Strehl,
- Vincent H.J. van der Velden,
- Vikki Rand,
- Stephen P. Hunger,
- Christine J. Harrison,
- Chris M. Bacon,
- Frederik W. van Delft,
- Mignon L. Loh,
- John Moppett,
- Josef Vormoor,
- Brian A. Walker,
- Anthony V. Moorman,
- Lisa J. Russell
Affiliations
- Simon Bomken
- Wolfson Childhood Cancer Centre, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom; The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne
- Amir Enshaei
- Wolfson Childhood Cancer Centre, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne
- Edward C. Schwalbe
- Department of Applied Sciences, Northumbria University, Newcastle upon Tyne
- Aneta Mikulasova
- Biosciences Institute, Newcastle University, Newcastle upon Tyne
- Yunfeng Dai
- Department of Biostatistics, Colleges of Medicine, Public Health and Health Professions, University of Florida, Gainesville, Florida
- Masood Zaka
- School of Health and Life Sciences, Teesside University, Middlesbrough, UK; National Horizons Centre, Teesside University, Darlington
- Kent T.M. Fung
- Wolfson Childhood Cancer Centre, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne
- Matthew Bashton
- The Hub for Biotechnology in the Built Environment, Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne
- Huezin Lim
- Wolfson Childhood Cancer Centre, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne
- Lisa Jones
- Wolfson Childhood Cancer Centre, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne
- Nefeli Karataraki
- Wolfson Childhood Cancer Centre, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne
- Emily Winterman
- Wolfson Childhood Cancer Centre, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne
- Cody Ashby
- Department of Biomedical Informatics / Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, Arkansas
- Andishe Attarbaschi
- St Anna Children's Hospital, Medical University of Vienna, Vienna
- Yves Bertrand
- Department of Institute of Hematology Oncology Pediatric (IHOP), Hospices Civils de Lyon, Lyon
- Jutta Bradtke
- Institute of Pathology, Department Cytogenetics, University Hospital Giessen and Marburg
- Barbara Buldini
- Maternal and Child Health Department, Padua University
- G.A. Amos Burke
- Department of Paediatric Haematology, Oncology, and Palliative Care, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Cambridge
- Giovanni Cazzaniga
- School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy; Centro Ricerca Tettamanti, University of Milano-Bicocca, Monza
- Gudrun Gohring
- Department of Human Genetics, Hannover Medical School, Hannover
- Hesta A. de Groot-Kruseman
- Dutch Childhood Oncology Group (DCOG), Utrecht, The Netherlands; Princess Maxima Center for Pediatric Oncology, Utrecht
- Claudia Haferlach
- MLL Munich Leukemia Laboratory, Munich
- Luca Lo Nigro
- Head of Cytogenetic-Cytofluorimetric-Molecular Biology Laboratory, Center of Pediatric Hematology Oncology, Azienda Policlinico "G. Rodolico - San Marco", Catania
- Mayur Parihar
- Department of Cytogenetics and Laboratory Haematology, Tata Medical Centre, Kolkata, India
- Adriana Plesa
- Hematology and Flow cytometry Laboratory, Lyon Sud University Hospital, Hospices Civils de Lyon, Lyon
- Emma Seaford
- Department of Paediatric Oncology, Bristol Royal Hospital for Children, Bristol
- Edwin Sonneveld
- Princess Maxima Center for Pediatric Oncology, Utrecht
- Sabine Strehl
- St. Anna Children's Cancer Research Institute, Vienna
- Vincent H.J. van der Velden
- Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam
- Vikki Rand
- School of Health and Life Sciences, Teesside University, Middlesbrough, UK; National Horizons Centre, Teesside University, Darlington
- Stephen P. Hunger
- Department of Pediatrics and the Center for Childhood Cancer Research, Children's Hospital of Philadelphia and the Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
- Christine J. Harrison
- Wolfson Childhood Cancer Centre, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne
- Chris M. Bacon
- Wolfson Childhood Cancer Centre, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom; The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne
- Frederik W. van Delft
- Wolfson Childhood Cancer Centre, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom; The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne
- Mignon L. Loh
- Department of Pediatrics, Benioff Children's Hospital and the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA
- John Moppett
- Department of Paediatric Oncology, Bristol Royal Hospital for Children, Bristol
- Josef Vormoor
- Wolfson Childhood Cancer Centre, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom; Princess Maxima Center for Pediatric Oncology, Utrecht
- Brian A. Walker
- Melvin and Bren Simon Comprehensive Cancer Center, Division of Hematology Oncology, Indiana University, Indianapolis, IN
- Anthony V. Moorman
- Wolfson Childhood Cancer Centre, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne
- Lisa J. Russell
- Wolfson Childhood Cancer Centre, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne
- DOI
- https://doi.org/10.3324/haematol.2021.280557
- Journal volume & issue
-
Vol. 108,
no. 3
Abstract
Rarely, immunophenotypically immature B-cell precursor acute lymphoblastic leukemia (BCP-ALL) carries an immunoglobulin- MYC rearrangement (IG-MYC-r). This can result in diagnostic confusion with Burkitt lymphoma/leukemia and use of individualized treatment schedules of unproven efficacy. Here we compare the molecular characteristics of these conditions and investigate historic clinical outcome data. We identified 90 cases registered in a national BCP-ALL clinical trial/registry. When present, diagnostic material underwent cytogenetic, exome, methylome and transcriptome analyses. The outcomes analyzed were 3-year event-free survival and overall survival. IG-MYC-r was identified in diverse cytogenetic backgrounds, co-existing with either established BCP-ALL-specific abnormalities (high hyperdiploidy, n=3; KMT2A-rearrangement, n=6; iAMP21, n=1; BCR-ABL1, n=1); BCL2/BCL6-rearrangements (n=15); or, most commonly, as the only defining feature (n=64). Within this final group, precursor-like V(D)J breakpoints predominated (8/9) and KRAS mutations were common (5/11). DNA methylation identified a cluster of V(D)J-rearranged cases, clearly distinct from Burkitt leukemia/lymphoma. Children with IG-MYC-r within that subgroup had a 3-year event-free survival of 47% and overall survival of 60%, representing a high-risk BCP-ALL. To develop effective management strategies this group of patients must be allowed access to contemporary, minimal residual disease-adapted, prospective clinical trial protocols.
